Paraproteinemic Neuropathy

Overview

A paraprotein is an abnormal antibody protein made in excess by a single clone of immune cells. When such a protein is present in the blood, it can sometimes interfere with the peripheral nerves, leading to paraproteinemic neuropathy. The abnormal protein may attack nerve components directly or deposit in the nerves, gradually disrupting their function.

This type of neuropathy is most often connected to a condition called monoclonal gammopathy of undetermined significance (MGUS), in which a paraprotein is present without a cancer. Less commonly, it is linked to blood disorders such as multiple myeloma, Waldenstrom macroglobulinemia, or amyloidosis. Identifying the underlying protein and any related disease is an important part of evaluation and treatment.

Symptoms

Symptoms usually develop slowly over months to years and often begin in the feet.

• Numbness and tingling, typically starting in the toes and feet
• A feeling of imbalance or unsteadiness when walking
• Tremor of the hands in some forms
• Weakness, often later and milder than the sensory symptoms
• Sensitivity or pain in the affected areas

Because the condition is gradual, many people first notice trouble with balance or fine hand movements. Sudden or rapidly worsening weakness is unusual and should be evaluated promptly.

Causes

The common thread is an abnormal antibody protein interfering with the nerves. The protein arises from one of several blood conditions.

• MGUS: The most frequent association, a noncancerous condition with a low level of paraprotein in the blood.
• Multiple myeloma: A cancer of plasma cells that overproduce abnormal protein.
• Waldenstrom macroglobulinemia: A blood cancer producing a specific large antibody protein.
• Amyloidosis: Abnormal protein deposits that can build up in and damage the nerves.

In some forms, the paraprotein specifically targets a component of the nerve's insulating myelin.

Risk Factors

• Older age, when paraproteins become more common
• A diagnosis of MGUS or a related plasma cell disorder
• A known blood cancer such as myeloma or Waldenstrom macroglobulinemia
• Amyloidosis

Diagnosis

Diagnosis links the nerve findings to an abnormal blood protein and identifies any underlying disease.

• Blood and urine protein tests: Special tests detect and characterize the paraprotein.
• Nerve conduction studies and EMG: Define the type and pattern of nerve damage.
• Bone marrow and imaging: Used to look for myeloma or related conditions when indicated.
• Nerve biopsy: Occasionally needed, for example to look for amyloid deposits.

Treatment

Treatment depends on the underlying condition and how disabling the neuropathy is.

• Treating the underlying disorder: When a blood cancer or amyloidosis is present, treating it can stabilize or improve the neuropathy.
• Immune therapies: For some paraprotein neuropathies, treatments that reduce the abnormal antibody may help selected patients.
• Monitoring: Mild, stable neuropathy linked to MGUS may simply be watched alongside the blood condition.
• Symptom relief: Medicines for nerve pain, physical therapy, and balance training to support daily function.

Responses vary by subtype, and some forms are slowly progressive despite treatment.

Living With the Condition

• There is no way to prevent the underlying paraprotein, but regular monitoring detects problems early
• If you have MGUS, attend follow-up so any related disease is caught promptly
• Use balance training and home-safety measures to reduce fall risk
• Report new or worsening symptoms so treatment can be reviewed
• Manage nerve pain with your doctor's guidance

When to See a Doctor

See a doctor for gradually worsening numbness, tingling, or unsteadiness, particularly if you are known to have a paraprotein or MGUS. Seek prompt evaluation if you develop:

• Worsening weakness or difficulty walking safely
• Rapid changes in sensation or strength
• Unexplained weight loss, bone pain, or fatigue, which may signal an underlying blood condition

Related Topics

Frequently Asked Questions

References

1. National Institute of Neurological Disorders and Stroke (NINDS). Peripheral Neuropathy.
2. Leukemia & Lymphoma Society. MGUS.
3. MedlinePlus, U.S. National Library of Medicine. Peripheral nerve disorders.
4. National Library of Medicine. StatPearls: Paraproteinemic Neuropathy.